Semi-automated human radiodosimetry extrapolation from small animal PET

Abstract

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Objectives: The main goal of this research was to test the utility of an approach incorporating semi-automated micro-PET mouse/digital atlas co-registration methods we previously developed for defining tracer bio-distribution (JNM, 2005;46:227P) in projecting effective organ doses for radiation exposure to humans.

Methods: Using software which co-registers a digital mouse phantom with a small animal PET mouse scan, enabling rapid semi-automated quantification of activity in organs, bio-distribution data were acquired from nine dynamic FDG small animal PET mouse scans. Bio-distribution estimates were extrapolated to a human model (standard man), using a previously established method (JNM, 1975;16:248-249) accounting for differences in relative organ masses, though not for species-related pharmacokinetic differences. A dose calculation software program based on MIRD schema was applied to obtain human organ dose estimates, which were compared with previously published FDG human dosimetry values (Radiation Dose Estimates for Radiopharmaceuticals: ORISE).

Results: We examined FDG small animal PET scans from nine mice. The organ-to-organ correlation coefficients (r) for the nine human dosimetry estimates versus the previously established human values ranged from 0.69 to 0.98 (median 0.96, average 0.97). The correlation resulting from the average activity distribution in the mice was 0.96. The extrapolation method identified the urinary bladder (0.12 mGy/MBq) as the target organ and the heart wall (0.05 mGy/MBq) as receiving the second highest radiation dose, both of which conformed to the established human organ distribution of FDG (0.19 and 0.06 mGy/MBq respectively). The estimated EDE was 0.025 mSv/MBq compared to the value of 0.030 mSv/MBq established in humans. Of the 21 other organs for which radiodosimetry exposure was estimated, 18 of the estimates were within ±0.01 mGy/MBq from the published dosimetry, and only 1 differed by more than 0.02 mSv/MBq (spleen).

Conclusions: A method was examined here to estimate in a semi-automated fashion human radiodosimetry from mouse data obtained from small animal PET. It generated reasonable correlations with previously published radiodosimetry values for biodistribution of FDG in humans. As dosimetric determinations are important for maximizing statistical quality of images while maintaining patient safety, these dose estimation methods may be used as a quick gauge of radiodosimetry for a new tracer. Such methods have the potential to be used in tracer development to save time and money, and decrease the number of animal specimens needed for initial testing purposes. Further investigations into interspecies extrapolation with methods similar to the ones we have utilized here may be of value in assessing the generalizability and limitations of such an approach.